Clinical characteristics of antidepressant use and related manic switch in bipolar disorder

Objectives:To examine the association between clinical and treatment characteristics and antidepressants (AD)-induced manic switch in bipolar disorder (BD).Methods:Total of 238 euthymic BD patients, who had been followed-up for at least 6 months at the outpatient clinic of Haseki Training and Research Hospital in istanbul, Turkey, were enrolled in this cross-sectional study in 2016. Semi-structured data form, the mood chart, and the mirror-designated assessment were applied to all subjects. The files of the patients were retrospectively reviewed and the patients using ADs were compared as AD-monotherapy (AD-m) and AD-combination (AD-c) groups, then divided into 2 subgroups according to the presence/absence of manic switch under AD treatment.Results:Fifty eight (47.15%) patients out of 123 who received ADs at least once had experienced a manic switch under AD treatment. The rate of manic switch in AD-m patients was significantly higher than the AD-c group. Independent from being monotherapy or combined treatment, AD use longer than 12 months was negatively associated with the occurrence of manic switch.Conclusion:Our study suggests that the risk of manic switch is especially prominent in the first months of AD use. Antidepressants use in combining it with a mood stabilizers (MS) may not be adequate in preventing switches in shorter terms. However, in longer term uses addition of MS to ADs may decrease the risk of switches.

Patients with bipolar disorder (BD) are found to live nearly half of their lives with depressive symptoms according to naturalistic observational research onto the illness course. Despite the occurrence of manic or hypomanic episodes, it is the hallmark defining the disorder, the predominance of depressive episodes over manic symptoms causes much of the significant morbidity, more serious harm on social function, and higher burden in BD.1 Nevertheless, treatment of bipolar depression has much less evident data and is far less optimized in clinical routine compared to the management of mania/hypomania. Although quetiapine and fluoxetine-olanzapine combination (OFC) are the 2 approved treatment options in bipolar depression, antidepressants (AD) have long been a focus of interest to challenge depressive episodes of BD.2 However, their efficacy and safety profile in BD is the subject of a long-standing dispute based on a scientific literature.3 Thus, the academicians endeavor to develop practice guidelines in light of relatively broad consensus.3,4 Accordingly, AD, as both combination or monotherapy, are not recommended for bipolar depression unless the depressive episode is very severe and has a poor response to MS, or antipsychotics (AP) monotherapy is shown.5,6 Despite the discourage from current treatment guidelines, ADs constitute 50% of all prescribed psychotropic agents in BD, and the long-term AD use is seen as high as 40% of all bipolar patients in the maintenance phase of the community health settings.6-8 Besides, the cardinal concern with the use of AD in the treatment of bipolar depression is that it may induce a switch to hypomania/mania. The recommendations above have hardly been supported by the relevant literature. Therefore, there is a need for further comprehensive research on the topic to elucidate clinical features and outcomes related to AD use in BD. Our aim in this study was to examine the frequency of AD use in BD, and assess the association between clinical and treatment characteristics, such as types of BD, presence of adjunctive treatment, AD types, AD treatment duration, and occurrence of mood switch in bipolar patients with a view to contributing evidence for a better understanding of the AD-related mood switch in BD. In light of the previous findings of relevant studies, we have addressed 2 major hypotheses that; 1) manic switches in BD would be closely linked to AD-monotherapy; 2) shorter use of ADs is associated with the higher occurrence of manic switch.     

The potential role of nutritional components in improving brain function among patients with Alzheimer’s disease: a meta-analysis of RCT studies

Objectives:To find out the potential role of nutritional components in improving brain function among patients with Alzheimer’s disease (AD).Methods:The correlation between nutrition and cerebral function in cases of AD has been the focus of 19 prospective randomised controlled trials (RCTs) with a combined research sample of 2297 patients. These RCTs are subject to systematic review and meta-analysis in the current paper.Results:Findings showed that chain-free secondary saturated fatty acids (SFA) and trans fatty acids (TFA) occurred in higher concentrations in AD patients’ brains than in controls. Furthermore, neuroinflammation was caused by remodelling of the lipid membrane and AD patients’ cognitive function was impacted by alterations in tyrosine, tryptophan, purine, and tocopherol pathway metabolomics. Moreover, in cases of mild-to-moderate AD, reduction in functionality was induced by administration of alpha-tocopherol for more than 12 months. Consumption of Souvenaid helps in synaptic synthesis, which enhances functional connectivity. Furthermore, consumption of the B vitamins folate, cobalamin and pyridoxine at dosages of 0.8 mg, 0.5 mg and 20 mg per day, respectively, over a period of one year resulted in lower plasma tHcy levels and brain atrophy.Conclusion:Chain-free SFA and TFA occur in greater amounts in the brains of individuals with AD than in those without AD.

Life expectancy has recently increased enormously throughout the world, owing to development in medical sciences. As a result, the ageing population has expanded quickly, causing a phenomenal rise in the prevalence of late-life cognitive diseases like AD and vascular dementia (VaD).1-3 Besides impacting cognition in ageing individuals, causing the brain to become atrophied and disrupting learning, cognitive, reasoning and communication capabilities, such conditions are also a significant burden from a social and economic perspective.4 Dementia occurs in 5-8% of people older than 65, 15-20% of those older than 75 and 25-50% of those older than 85 years of age.5 Age, gender, head trauma and CVD risk factors (e. g. cardiac disease, diabetes, high blood pressure, depression, high cholesterol, sedentarism, smoking, alcohol drinking) are among the known sporadic AD risk factors that are not of genetic origin.6-8The creation of medication capable of deferring AD onset by disrupting and mitigating Aβ synthesis has been the aim of a number of clinical research trials and empirical work and has attracted ample annual investment from pharmaceutical companies. Even though such medication is yet to be formulated, drugs for symptom management do exist.9 Thus, the approach toward drug development for AD, as well as the therapeutic role of nutrition in preventing AD, need to be reconsidered.Evidence has been produced that AD risk and progression are diminished by diet-related components like antioxidants,10,11 vitamins,12-14 polyphenols,15,16 and omega-3 fatty acids.17,18 By contrast, saturated fatty acids19 and simple carbohydrates20 are considered to increase likelihood of AD development.21 The RCTs carried out in the period 2010-2018 were reviewed in this paper to investigate whether AD patients’ cognitive function can be enhanced based on nutritional constituents. To this end, a meta-analysis was conducted to establish the extent to which cerebral function in AD cases was influenced by nutrition-based treatments. Furthermore, subgroup meta-analyses were also carried out to determine conformance to nutrition plans, proportion of deaths due to general causes and AD, respectively, body weight (BW), lean body mass (LBW), life expectancy, quality of life (QoL), and development of additional neurodegenerative diseases.     

Escitalopram for agitation in Alzheimer's disease (S-CitAD): Methods and design of an investigator-initiated,randomized, controlled,multicenter clinical trial

IntroductionAlzheimer's disease (AD) is a disabling, common cause of dementia, and agitation is one of the most common and distressing symptoms for patients with AD. Escitalopram for agitation in Alzheimer's disease (S-CitAD) tests a novel, clinically derived therapeutic approach to treat agitation in patients with AD.MethodsS-CitAD is a NIH-funded, investigator-initiated, randomized, multicenter clinical trial. Participants receive a structured psychosocial intervention (PSI) as standard of care. Participants without sufficient response to PSI are randomized to receive 15 mg escitalopram/day or a matching placebo in addition to PSI. Primary outcome is the Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (mADCS-CGIC).DiscussionS-CitAD will provide information about a practical, immediately available approach to treating agitation in patients with AD. S-CitAD may become a model of how to evaluate and predict treatment response in patients with AD and agitation as a neuropsychiatric symptom (ClinicalTrials.gov Identifier: NCT03108846).     

Genetic origin of a large family with a novel PSEN1 mutation (Ile416Thr)

IntroductionA small percentage of Alzheimer's disease (AD) cases are caused by genetic mutations with autosomal dominant inheritance. We report a family with a novel variant in PSEN1.MethodsWe performed clinical and genetic evaluation of 93 related individuals from a Colombian admixed population. 31 individuals had whole-genome sequencing.ResultsGenetic analysis revealed a missense variant in PSEN1 (NM_000021.3: c.1247T>C p.Ile416Thr), which originated on an African haplotype and segregated with AD logarithm of the odds score of 6. Their clinical phenotype is similar to sporadic AD except for earlier age at onset: the mean age at onset for mild cognitive impairment was 47.6 years (standard deviation 5.83) and for dementia 51.6 years (standard deviation 5.03).DiscussionIle416Thr is a novel pathogenic variant that causes AD in the sixth decade of life. The history of the region that included slave importation and admixtures within a confined geographic locale represents a “mini-population bottleneck” and subsequent emergence of a rare dominant mutation.     

Multidomain intervention and/or omega-3 in nondemented elderly subjects according to amyloid status

IntroductionThe Multidomain Alzheimer Preventive Trial (MAPT) assessed the efficacy of omega-3 fatty acid supplementation, a multidomain intervention (MI), or a combination of both on cognition. Impact according to cerebral amyloid status was evaluated by PET scan.MethodsParticipants were nondemented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. The primary outcome was a change from baseline in 36 months measured with a cognitive composite Z score.ResultsNo effect was observed on cognition in the negative amyloid group (n = 167). In the positive amyloid group (n = 102), we observed a difference of 0.708 and 0.471 in the cognitive composite score between the MI plus omega-3 fatty acid group, the MI alone group, and the placebo group, respectively.DiscussionMI alone or in combination with omega-3 fatty acids was associated with improved primary cognitive outcome in subjects with positive amyloid status.Trial RegistrationClinicalTrials.gov Identifier: NCT01513252.     

Prevalence and risk factors of myasthenia gravis recurrence post-thymectomy

Objectives:To evaluate the prevalence and the factors associated with recurrence of myasthenia gravis following thymectomy.Methods:Six electronic databases which reported on recurrence of myasthenia gravis following thymectomy and/or its risk factors from 1985 to 2018 were searched. Summary prevalence and risk values obtained based on the random effect models were reported.Results:Seventy (70) papers containing 7,287 individuals with myasthenia gravis who received thymectomy as part of their management were retrieved. The patients had a mean follow-up of 4.65 years post-thymectomy. The prevalence of myasthenia gravis recurrence post-thymectomy was 18.0% (95% CI 14.7–22.0%; 1865/7287). Evident heterogeneity was observed (I²=93.6%; p<0.001). Recurrence rate was insignificantly higher in male compared with female patients (31.3 vs. 23.8%; p=0.104). Pooled recurrence rates for thymomatous (33.3%) was higher than the rate among non-thymomatous (20.8%) myasthenia gravis patients (Q=4.19, p=0.041). Risk factors for recurrence include older age, male sex, disease severity, having thymomatous myasthenia gravis, longer duration of the myasthenia gravis before surgery, and having an ectopic thymic tissue.Conclusion:A fifth of individuals with myasthenia gravis experience recurrence after thymectomy. Closer monitoring should be given to at-risk patients and further studies are needed to understand interventions to address these risks.

Myasthenia gravis (MG) a rare clinical condition characterized by autoimmune abnormalities is also the commonest neuromuscular junction (NMJ) disorder.1 Its pathophysiology involves the production of abnormal antibodies which binds to nicotinic acetylcholine receptors at the NMJ of skeletal muscles leading to alteration and damage of the NMJ.1-2 The disease is common in young women, however, another peak in incidence may occur at the 6th or 7th decade of life mainly in men in some population; and it may exhibits no sex preference in others.2 Clinically, patients with MG develop varying levels of skeletal muscle weakness affecting the ocular, bulbar, oculo-bulbar system, respiratory system, and the extremities.1 The pattern and course of MG is complex, varying from early remission to acute exacerbation and even death.3Previous research has revealed a strong relation between MG and disorders affecting the thymus. About 40 to 70% of individuals with MG have thymic follicular hyperplasia, and 10 to 21% of them have thymoma.4-6 Also, 20-47% of individuals having a thymoma have already developed or will develop MG.6-7 Findings from the literature indicate that 40 to 90% of individuals with MG attained remission following thymectomy compared with 10 to 20% among individuals with MG treated with medications without any surgery.6,8 Also, a recent randomised controlled trial demonstrated that thymectomy for individuals with nonthymomatous MG demonstrated better treatment outcomes during a three-year period compared with pharmacological therapy alone.9 Thus, guidelines now recommend thymectomy as a key treatment approach for MG.10A number of systematic reviews and/or meta-analyses among individuals with MG have been carried out. Some of these reviews explored the differences in outcomes between thymectomy and conservative management of MG,11,12 others compared surgical approaches of thymectomy,13-15 or potential prognostic factors for remission among individuals with MG irrespective of histological type following thymectomy.3,16 None assessed recurrence of MG following thymectomy or its risk factors. The identification of patient factors which are associated with recurrence of MG following thymectomy is crucial for the development of targeted interventions to address challenges associated with the care of individuals with MG. This systematic review and meta-analysis aimed to estimate the post-thymectomy recurrence rates and to investigate the factors associated with recurrence of MG following thymectomy in individuals with MG.     

Evaluation of memory endophenotypes for association with CLU,CR1, and PICALM variants in black and white subjects

BackgroundGenetic variants at the CLU, CR1, and PICALM loci associate with risk for late-onset Alzheimer's disease (LOAD) in genomewide association studies. In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in black and white subjects.MethodsWe pursued an association study between single nucleotide polymorphism genotypes at the CLU, CR1, and PICALM loci and memory endophenotypes. We assessed black subjects (AA series: 44 with LOAD and 224 control subjects) recruited at Mayo Clinic Florida and whites recruited at Mayo Clinic Minnesota (RS series: 372 with LOAD and 1690 control subjects) and Florida (JS series: 60 with LOAD and 529 control subjects). Single nucleotide polymorphisms at the LOAD risk loci CLU (rs11136000), CR1 (rs6656401, rs3818361), and PICALM (rs3851179) were genotyped and tested for association with Logical Memory immediate recall, Logical Memory delayed recall, Logical Memory percent retention, Visual Reproduction immediate recall, Visual Reproduction delayed recall, and Visual Reproduction percent retention scores from the Wechsler Memory Scale–Revised using multivariable linear regression analysis, adjusting for age at exam, sex, education, and apolipoprotein E ε4 dosage.ResultsWe identified nominally significant or suggestive associations between the LOAD-risky CR1 variants and worse Logical Memory immediate recall scores in blacks (P = .068–.046, β = −2.7 to −1.2). The LOAD-protective CLU variant is associated with better logical memory endophenotypes in white subjects (P = .099–.027, β = 0.31–0.93). The CR1 associations persisted when the control subjects from the AA series were assessed separately. The CLU associations appeared to be driven by one of the white series (RS) and were also observed when the control subset from RS was analyzed.ConclusionThese results suggest for the first time that LOAD risk variants at CR1 may influence memory endophenotypes in blacks. In addition, the CLU LOAD-protective variant may confer enhanced memory in whites. Although these results would not remain significant after stringent corrections for multiple testing, they need to be considered in the context of the LOAD associations with which they have biological consistency. They also provide estimates for effect sizes on memory endophenotypes that could guide future studies. The detection of memory effects for these variants in clinically normal subjects, implies that these LOAD risk loci might modify memory prior to clinical diagnosis of AD.     

Spectrum of medulloblastoma subtypes and frequency of MYC amplification; Experience from a tertiary care center in Saudi Arabia

Objectives:To clarify the spectrum of morphological and molecular subtypes of medulloblastoma (MBL), in addition to MYC and MYCN amplification statuses in a cohort of Saudi patients. The latter was correlated with patient outcome.Methods:We conducted a retrospective cohort study of 57 patients with MBL, diagnosed at the central laboratory of King Abdulaziz Medical City in Riyadh, Saudi Arabia, between 2006 and 2019. Molecular analysis for MYC and MYCN amplification was performed for the 19 most recently diagnosed patients.Results:Classic MBL was the most prevalent histologic subtype and MBL with extensive nodularity was the rarest. The non-WNT/non-SHH molecular subgroup was the most common while the WNT-activated was the least common. Among 19 patients analyzed, MYC and MYCN amplifications were discovered in 2 (10.5%) and 1 (5.3%) cases, respectively, using interphase fluorescence in-situ hybridization. The 2 MYC amplified cases belonged to the large cell/anaplastic subtype and had the worst outcomes.Conclusion:The MYC amplification corresponded with poor prognosis, the large cell/anaplastic variant of MBL, and the non-WNT/non-SHH molecular subtype.

Medulloblastoma (MBL) is the most prevalent pediatric embryonal brain neoplasm originating from the cerebellum and dorsal brain stem.1 There are 4 histomorphological variants of MBL: classic, desmoplastic/nodular, large cell/anaplastic, and MBL with extensive nodularity.1–3 The MBLs are now classified into 4 molecular subtypes: Wingless (WNT)-activated, sonic hedgehog (SHH)-activated, group 3, and group 4. Groups 3 and 4 are less well defined from a molecular standpoint, and are difficult to distinguish from each other using commercially available surrogate biomarkers.4 For practical purposes, MBLs are therefore subdivided into 3 molecular subgroups: WNT-activated, SHH-activated, and non-WNT/non-SHH.Traditionally, patients with MBL were stratified according to their risk of recurrence (average risk: >3 years of age, no/minimal residual disease post-surgery, and no CNS metastasis; and high risk: <3 years of age exclusive to the extensively nodular subtype, significant residual disease post-surgery, and evidence of metastasis within the CNS).4The MYC amplifications have long been associated with highly aggressive MBLs, and occur in 5% to 10% of MBLs.5 The purpose of this study was to recognize the spectrum of MBL histologic and molecular subtypes seen at our institute and to estimate the frequency of MYC and MYCN amplification. Additionally, the prognosis of the MYC amplified cases was compared to that of their non-amplified counterparts.     

The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population

In the present study, we investigated whether polymorphism of ARNTL2 (BMAL2) gene rs2306074 T/C was associated with susceptibility of Alzheimer disease (AD) in Chinese population. A case–control method was employed in this study. 296 unrelated AD patients and 423 control subjects were recruited in current study. The prevalence of C carriers in BMAL2 gene rs2306074 T/C in AD patients was significantly higher than that of control subjects in both the whole sample and APOE ε 4 non-carriers (in the whole sample: χ ² = 5.938, P = 0.012; in APOE ε 4 non-carriers: χ ² = 9.048, P < 0.0001). In addition, both in the whole sample and APOE ε 4 non-carriers, prevalence of CC genotypes in BMAL2 gene rs2306074 of AD patients was also significantly higher than that in controls (in the whole sample: χ ² = 5.126, P = 0.018; in APOE ε 4 non-carriers: χ ² = 7.389, P = 0.023). However, there was no significant difference of prevalence of C carriers and CC genotypes in BMAL2 gene rs2306074 T/C between AD patients and control subjects among APOE ε 4 carriers (C carriers: χ ² = 0.020, P = 0.900; CC genotypes: χ ² = 0.017, P = 0.946). C carriers in BMAL2 gene rs2306074 T/C are associated with a high susceptibility of AD among APOE ε 4 non-carriers but not among APOE ε 4 carriers in Chinese population.     

Rural stakeholder perceptions about cognitive screening

Abstract

Objectives: The study aims were to explore stakeholder perceptions about cognitive screening in a rural, ethnically diverse, underserved setting, and to examine whether perceptions varied by years lived in a rural area, career, health literacy, willingness to be screened, ethnicity, education, or age.

Methods: Twenty-one rural, ethnically diverse stakeholders completed an open-ended interview of five questions and a measure regarding perceptions about cognitive screening (PRISM-PC, Boustani, et al., 2008 Boustani, M., Perkins, A. J., Monahan, P., Fox, C., Watson, L., Hopkins, J., … Hendrie, H. C. (2008). Measuring primary care patients’ attitudes about Alzheimer’s disease. International Journal of Geriatric Psychiatry, 23(8), 812–820. doi:10.1002/gps.1983.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Open coding using the in vivo process (Saldaña, 2015 Saldaña, J. (2015). The coding manual for qualitative researchers. CA: Sage Publications.  [Google Scholar]) to “derive codes from the actual participant language” (p. 77) was used to analyze the qualitative data. We used Pearson correlation to examine relationships between the PRISM-PC and sociodemographics including age, years of education, health literacy, years lived in rural areas, and willingness to participate in cognitive screening.

Results: Eight codes and two themes were identified from the in vivo analysis. The eight codes were “a sentence being pronounced over the lives”, “keep everybody at home”, “Education is big”, the trust issues is everything here”, “identify support systems”, “access to care”, and “there is a cost to do that”. The two themes were “Trust is the essential component of connecting with Community”, and (2) “The Community recognizes the importance of knowledge in improving care. PRISM-PC results added new information in that persons were concerned about the emotional and financial burden on their families. Overall, regardless of age, careers, care involvement, health literacy, or education, 81% of stakeholders indicated they would seek annual cognitive screening.

Discussion: It is important for rural health professionals to consider that contrary to previous stigma concerns, stakeholders may support earlier dementia detection.     

Visual evoked potentials follow-up in idiopathic intracranial hypertension

Objectives:To demonstrate the importance of visual evoked potential (VEP) in determining the severity and prognosis of the disease and in monitoring the clinical course in patients with idiopathic intracranial hypertension (IIH).Methods:This is a prospective cross-sectional study conducted covering the period between March 2014 and January 2015. The study included 32 patients recently diagnosed with IIH and 30 healthy volunteers. The initial VEP values of the IIH patients were compared to the VEP values of the healthy control group. Furthermore, the initial VEP values of the IIH patients were compared with their VEP values after one month of treatment.Results:The mean age of the IIH patients was 37.8±12.02 years. Of the IIH patients, 27 (84%) were females and 5 (16%) were males. There was a statistically significant association of the initial VEP values with the visual field findings (p=0.011) and visual acuity (p=0.040). Moreover, a statistically significant difference was found between the control group and IIH patients in terms of right (p<0.001) and left P100 values (p<0.001). While 18 (56%) of the initial VEPs of IIH patients were pathological, 14 (44%) of the second VEPs were pathological, and this difference was not statistically significant (p=0.125).Conclusion:A relationship between the VEP P100 values and the severity of the disease was detected, while the importance of monitoring VEP values in the follow-up of IIH patients was not demonstrated.

Idiopathic intracranial hypertension can be defined as raised intracranial pressure with a normal cerebrospinal fluid (CSF).1,2 The overall incidence of IIH is 2.4/100,000; however, the incidence is 22/100,000 in obese women.3 Indeed, the female gender and a high body mass index (BMI) are important risk factors for the disease and female patients account for 90% of the cases.4,5The visual field is commonly affected in IIH patients.6 Although the visual field is currently the most sensitive method to monitor visual disturbances during the course of the disease, its specificity and sensitivity is not 100%.6,7 However, an early diagnosis, determination of the disease severity, and follow-up of the patients with IIH are critical as IIH can cause serious and irreversible visual field defects and even vision loss during the course of the disease.7-9The number of patients with IIH is on the rise globally as the number of patients with obesity increases day by day.10 There is a paucity of precisely sensitive and objective indicators of the disease for monitoring relapses and remission.11,12 Moreover, no sensitive and objective methods have been established yet to determine the disease severity in order to decide whether surgery should be performed in these patients.12-14Despite the potential of IIH to cause visual morbidity, only a limited number of studies are available in the literature to predict the potential impact of IIH on the vision.13 The findings obtained by VEP reflect the functions of the visual pathways extending from the retina to the occipital cortex. The test is particularly sensitive to demonstrate conduction disturbances in the anterior (pre-chiasmatic) visual pathway.15,16 A few studies have shown abnormal findings in VEP tests in patients with IIH, indicating the importance of VEP in the evaluation of the visual functions.17 In the literature, we found only one study evaluating the value of VEP values in the follow-up of patients with IIH.17This study aimed to demonstrate the importance of VEP testing in determining the severity and prognosis of the disease and in monitoring the clinical course of the patients with IIH as the number of studies evaluating this subject is limited in the literature.     

A systematic review of adults’ sitting balance assessments in neurological and neuromuscular conditions

Objectives:To find out new assessment tools for sitting, in patients with neurological and neuromuscular conditions, to be recommended for rehabilitation practice locally in Saudi Arabia and internationally.Methods:Four databases were used: PubMed, Web of Science, Ovid Medline, and Cochrane. Inclusion criteria were articles published between the years 2009–2019; sitting, not standing or walking; assessment not intervention; published in English and studies on adults only. Exclusion criteria were any assessment that measures the standing/walking ability or has items for that, and studies that include pediatric or adolescent or both.Results:Ten articles met our criteria including 464 patients and divided into 3 main neurological conditions (stroke, SCI, and MS). One assessment (Function in Sitting Test) showed promising potential being implemented with both stroke and multiple sclerosis, Cronbach’s alpha, α were 0.91 and 0.98 indicating high internal consistency. It was used with SCI patients, however, no access was available to include this study in this review.Conclusion:This review indicates an extension of what was carried out by previous systematic reviews with neurological conditions. It seems that Function in Sitting Test is the most frequent assessment in this review with multiple neurological conditions (stroke, MS and SCI) with high internal consistency and high quality studies according to available data. However, this review showed that there is an absence of evidence for individuals with brain injury. Further work needs to be carried out to address such groups of patients to extend the choices that clinicians can use in rehabilitation sittings.

Setting balance is one of the most important factors in activities of daily living (ADL) performance; it allows patients to engage safely and effectively in selected tasks. Sitting components are varied in the literature between assessing the trunk control as a system that contributes to sitting and addressing the actual sitting attribute via objective measures of functional tasks. One systematic review highlighted this for neurological conditions e.g., (stroke, Parkinson disease and multiple scleroses).1 Another one discussed this for spinal cord injury conditions.2 Both found a total of 31 instruments, with no clear conclusion about an instrument that can be used with the various neurological conditions that address sitting only. Thus, our review is aiming to see if there are any new tools after previous published systematic reviews1 and2 for various neurological conditions and whether the neuromuscular condition has any assessments that capture sitting as a body function and structure impairment resulting from health condition according to the international classification of functioning model ICF.3 Primary investigator (WA) used to work in a rehabilitation sitting when this review was started and search term was run for the first time in September 2018. Therefore, finding new assessment tools for sitting, in patients with neurological or neuromuscular conditions was important for the practice. Furthermore, the result of this review would be an update recommendation, for colleagues who work in mixed in or outpatient units in rehabilitation practice. With various neurological conditions locally and internationally.MethodsEligibility criteriaData were collected depending on the following inclusion criteria; population are adult with neurological impairment (stroke, TBI, SCI, MS, ALS, CP and N-TBI). Interventions included are assessment of sitting balance (objective and subjective). No comparison group has been chosen. Outcomes are psychometrics properties. Our review focuses on English language only (Table 1). Articles should be published between 2009–2019. Exclusion criteria are any assessment that measures the standing/walking ability or has items for that, and studies that include pediatric or adolescent or both. Pediatric or adolescent population have been excluded due to the primary investigator’s experience (WA), which was with adult only with different neurological conditions.Table 1PICO components of the review.

Corpus callosum index correlates with brain volumetry and disability in multiple sclerosis patients

Objectives:To analyze the correlation between corpus callosum index (CCI), brain volumetry, and disability in multiple sclerosis (MS) patients. The brain volumetry consists of the corpus callosum, cortical gray matter, subcortical gray matter, and white matter volumes.Methods:This was a retrospective cross-sectional study from October 2018 to February 2019 of 30 patients with MS aged 20 to 61 years old. Brain volumetry was performed using FreeSurfer© software. The CCI were measured manually using conventional best mid-sagittal T1W brain MRI. The anterior, posterior, and medium segments were measured and divided to its greatest anteroposterior diameter. Higher CCI values indicated greater corpus callosum volumes. Clinical evaluation was comprised of MS subtype, age of onset, relapse frequency and Expanded Disability Status Scale (EDSS).Results:Thirty MS patients with median of age 22 years were included. Relapsing-remitting (RRMS) subtype were 73.3%. Very significant correlations were shown between the CCI and corpus callosum volume (CCV) (r=0.79; p<0.0001) and cerebral white matter volume (r=0.81; p<0.0001). Significant correlations were shown between the CCI and cortical gray matter volume (r=0.64; p<0.0001) and subcortical gray matter volume (r=0.69; p<0.0001). The CCI was positively correlated with age of onset and inversely with EDSS. The CCV and CCI were smaller in secondary progressive MS (SPMS).Conclusion:The CCI is easy and fast to obtain in conventional MRI and significantly correlated with brain volumetry, age of onset and disability in MS patients.

Multiple sclerosis (MS) is one of the most common neurological diseases of the central nervous system and has various clinical manifestations, affecting the sensory, motor, cerebellar, brainstem, and autonomic systems.1–4 The MS progression will lead to disability that can affect the quality of life. In 2013, the prevalence of MS was 33 per 100,000 globally, an increase from approximately 30 per 100,000 in 2008.5 Regarding the cognitive impairment, it has been found in a study by Rao et al6 a 45% frequency of cognitive impairment in MS patients. Furthermore, it has been found in several studies that the decline in visual and verbal episodic memory as well as decelerated cognitive processing speed are the most frequent cognitive domains impaired in multiple sclerosis.7 Between these 2 domains, it has been shown that memory impairment were slightly more common than those with memory impairment and processing speed impairment in 128 patients with relapsing-remitting MS (RRMS).8 In our previous study, we found impairments in the Symbol Digit Modality test (up to 50%), California Verbal Learning test-II (27.5%), and Brief Visuospatial Memory test-revised (32.5%) in MS patients.9Brain volume in MS patients were found to be significantly smaller compared to healthy subjects and associated with the progression of disability.10 Brain atrophy in MS can occur by 3 mechanisms: volume loss within the lesion itself, retrograde degeneration, and Wallerian degeneration in the remote area of the fiber pathway.4,11,12 Brain atrophy can be seen in earliest stages of MS (clinically isolated syndrome).13 Gray matter atrophy begins early in the course of the disease and is correlated with the progression of disability, especially motor and cognitive disability.14–16 Measuring brain atrophy has been proposed as one of several treatment monitoring parameters for MS.17The corpus callosum is one of the main white matter pathways and affected by the progress of chronic diseases, including MS.1,3,4 Corpus callosum damage is correlated with cognitive impairment and motor disability in MS patients. Corpus callosum atrophy could be a clinically relevant marker of cognitive impairment.18–20Brain volumetry using magnetic resonance imaging (MRI) is a useful, noninvasive tool in assessing subcortical morphometric changes as well as evaluating the regional neurological impact of psychopathology, such as dementia, psychiatric disorders, and normal aging.21 Some software packages have been developed for measuring brain tissue volume using MRI with semi-automatic segmentation, such as FreeSurfer© (The General Hospital Corporation, Boston MA, USA), FIRST (FMRIB’s Integrated Registration and Segmentation Tool), FSL (FMRIB’s Software Library), and SPM (Statistical Parametric Mapping).22With this background, the objective of this study was to determine the correlation between the corpus callosum index (CCI) measurements and the corpus callosum, cortical gray matter, subcortical gray, and cerebral white matter volumes determined through brain MRI volumetry and clinical characteristics in MS patients.     

Inflammatory bowel disease and restless leg syndrome

Objectives:Inflammatory bowel disease (IBD) has been associated with restless leg syndrome (RLS). This study aims to explore the prevalence, clinical predictors, and severity of RLS in IBD patients compared to controls.Methods:We conducted a case-control study between January and December of 2019 comparing IBD patients with controls. Assessment of RLS was performed using the previously validated diagnostic restless leg syndrome questionnaire (RLSQ). Logistic regression analyses were applied to investigate associations between patient demographics and clinical features and RLS diagnosis.Results:A total of 218 IBD patients and 211 healthy controls were incorporated after excluding 6 patients with positional discomfort and 4 patients with habitual foot tapping. The mean age was 30.2±11.7 and 64% were females. The prevalence of RLS was 16/218 (7.34%) and 17/211 (8.06%) among cases and controls, respectively. Based on the RLSQ severity score, 6/16 (37.5%), 4/16 (25%) and 1/16 (6.3%) of the IBD patients with RLS had mild, moderate and severe RLS; respectively. The odds of IBD were lower among patients with confirmed RLS (OR=0.90, 95% CI=0.44-1.84, p = 0.78). In the logistic regression analysis, only vitamin B12 deficiency (OR=10.20, 95% CI=1.40-74.10, p = 0.022) was associated with RLS diagnosis among IBD patients.Conclusion:No difference was found in the prevalence of RLS between IBD patients and non-IBD controls. Vitamin B12 deficiency was associated with RLS diagnosis among patients with IBD.

Inflammatory bowel disease (IBD) is a family of chronic inflammatory disorders that cause inflammation of the gastrointestinal tract. It comprises two main conditions: ulcerative colitis (UC) and Crohn’s disease (CD). Approximately 30% of IBD patients suffer from extra-intestinal manifestations (EIMs), which can involve the rheumatologic, musculo-cutaneous, and hepato-biliary systems.1,2 Anemia is a common manifestation of IBD that can be attributed to iron, folate (folic acid), or vitamin B12 deficiencies.3Patients with IBD may develop neurological symptoms as part of the disease itself or through secondary complications, such as anemia. Perhaps one of its most distressing neurological manifestations is restless leg syndrome (RLS), which is a movement disorder characterized by an uncomfortable sensation in the legs which engenders restlessness temporarily relieved by movement. This discomfort takes place most commonly during night and when resting, and often disturbs sleep.4 Iron deficiency anemia (IDA) has been strongly associated with RLS.5,6 The RLS can be primary, i.e., idiopathic, or secondary, and is believed to be caused by both genetic and environmental factors.7 The most common secondary causes of RLS include iron deficiency and kidney disease; other causes include cardiovascular disease, arterial hypertension, diabetes, liver cirrhosis, migraine, Parkinson’s disease, and pregnancy.7-9 In a previous study conducted in Saudi Arabia, the prevalence of RLS among IBD patients was estimated to be 21.5%, compared to 9.7% in controls.10 Another study reported a 10% prevalence rate of RLS in North America and Europe, which is much higher than the prevalence rate reported by studies from Asian countries (0.6-1.8%).9 In contrast to many findings in Asian countries, the prevalence of RLS has been reported to increase with age in Europe, North America, and Saudi Arabia,10,11 and women have a higher prevalence of RLS compared to men.11,12 Moreover, it has been suggested that patients with RLS have poorer health and quality of life.11 This study describes the prevalence, clinical predictors, and severity of RLS in IBD patients compared with healthy controls.     

Association between cranial asymmetry severity and chronic subdural hematoma laterality

Objectives:To analyze the association between cranial asymmetry severity and chronic subdural hematoma (CSDH) laterality.Methods:We retrospectively assessed 120 patients with surgically treated unilateral CSDH from January 2009 to December 2018. Preoperative computed tomography images were used to determine occipital vault angles, bilateral cranium areas, and cranial index of symmetry (CIS) ratios.Results:The male sex (70%) was the predominant factor promoting CSDH pathogenesis. In the overall study population (mean age, 71.3 years; left-sided CSDH, 58/120 [48%] patients; right-sided CSDH due to right-sided flat cranium, 38 patients; left-sided CSDH due to right-sided flat cranium, 37 patients). Flat cranial asymmetry was nonsignificantly associated with CSDH laterality (p- value=.689). However, most CSDH patients (86.7% of 120 patients) presented dominant-sided nonoverlapping areas on the left side. Thirteen (81.3%) patients presenting right-dominant nonoverlapping areas had right-sided CSDH, and 55 (52.9%) patients had left-dominant nonoverlapping area had left-sided CSDH (p- value=0.01). The CIS ratio was significantly higher in patients with right-dominant nonoverlapping areas than in those with left-dominant nonoverlapping areas (97.2% vs 95.9%, p- value<0.0001).Conclusion:Left-sided hematoma predominance is not associated with a flat cranium and laterality of unilateral CSDH. Moreover, more asymmetric crania with lower CIS ratios may predict left-sided CSDHs, whereas the right-sided CSDHs may be more common in symmetric crania with higher CIS ratios. The CSDH laterality is potentially attributable to cranial asymmetry severity.

Chronic subdural hematoma (CSDH), a common neurosurgical entity, is considered a delayed manifestation of head trauma, occurring mostly in older men.1 Although CSDHs can occur in unilateral or bilateral intracranial spaces, left-sided predominance has been previously reported.2,3 Few studies have reported that cranial morphology and gravity contribute to the laterality of CSDH.4–6 Cranial asymmetry is more common among crania flattened toward the right side, influencing the left-sided predominance of CSDH.6 The cranial index of symmetry (CIS) with a semiautomated method has been introduced to objectively determine the severity of cranial deformations including plagiocephaly.7 A preliminary study reported that the objective nonradiographic method potentially serves as an unbiased measurement of cranial asymmetry.7 The flat side has been simply defined by a smaller angle through a simple method considering angles among 3 lines.4–6 However, the angles may be manually affected by the points of the intersection of the manually selected lines, thus obstructing cranial asymmetry assessment. Therefore, here, we aimed to clarify the association between the severity of cranial asymmetry and the laterality of CSDH by using an objective semiautomated method.     

Mayo's Older Americans Normative Studies: Age- and IQ-Adjusted Norms for the Wechsler Memory Scale--Revised

ABSTRACT

Normative data sets for standardized neuropsychometric instruments often include adjustments for subject variables. There are reasons to believe, however, that improvements in interpretive accuracy that result from such adjustments are less than optimal. In particular, “years of formal education” may be less closely related to test performances than is general intellectual functioning. In this third of four reanalyses of results from the Mayo Clinic's Older Americans Normative Studies (MOANS) databases, age-adjusted index and scaled scores for the Wechsler Memory Scale-Revised were found to be more strongly associated with Mayo age-adjusted WAIS-R Full Scale IQ scores (rs = .271 to .631) than with education (rs = .089 to .310) for healthy older examinees between 56 and 99 years of age. These associations were strongest for Attention/Concentration and General Memory Index scores and, in general, for individuals with average intelligence (cf. Dodrill, 1997 Dodrill , C. B. ( 1997 ). Myths of neuropsychology . The Clinical Neuropsychologist , 11 , 1 – 17 .[Taylor & Francis Online], [Web of Science ®] , [Google Scholar] 1999 Dodrill , C. B. ( 1999 ). Myths of neuropsychology: Further considerations . The Clinical Neuropsychologist , 13 , 562 – 572 . [PUBMED] [INFOTRIEVE] [CSA] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]). Tables of age- and IQ-adjusted percentile equivalents of Mayo age-adjusted WMS-R index scores and MOANS age-adjusted WMS-R subtest scaled scores are presented for eleven age ranges and seven IQ ranges.     

Older and younger adults differently judge the similarity between negative affect terms

Objectives: Theoretical models of aging suggest changes across the adult lifespan in the capacity to differentiate emotions. Greater emotion differentiation is associated with advantages in terms of emotion regulation and emotion resiliency. This study utilized a novel method that directly measures judgments of affect differentiation and does not confound affective experience with knowledge about affect terms. Theoretical predictions that older adults would distinguish more between affect terms than younger persons were tested.

Method: Older (n = 27; aged 60–92) and younger (n = 56; aged 18–32) adults rated the difference versus similarity of 16 affect terms from the Kessler and Staudinger (2009 Kessler, E. M., &; Staudinger, U. M. (2009). Affective experience in adulthood and old age: The role of affective arousal and perceived affect regulation. Psychology and Aging, 24, 349–362.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) scales; each of the 16 items was paired with every other item for a total of 120 ratings. Participants provided self-reports of trait emotions, alexithymia, and depressive symptoms.

Results: Older adults significantly differentiated more between low arousal and high arousal negative affect (NA) items than younger persons. Depressive symptoms were associated with similarity ratings across and within valence and arousal.

Conclusion: Findings offer partial support for theoretical predictions that older adults differentiate more between affect terms than younger persons. To the extent that differentiating between negative affects can aid in emotion regulation, older adults may have an advantage over younger persons. Future research should investigate mechanisms that underlie age group differences in emotion differentiation.     

Decreased serum uric acid in patients with traumatic brain injury or after cerebral tumor surgery

Objectives:To investigate changes in sUA in patients with TBI or patients after cerebral tumor surgery and the possible mechanism of these changes.Methods:This prospective cohort study enrolled patients with TBI or underwent cerebral tumor surgery at West China Hospital, China, from November 2014 to May 2018. Serum UA (sUA) levels, urine excretion, UA oxidant product allantoin and other clinical parameters were assessed.Results:100 patients were enrolled for analysis. sUA in patients with TBI or underwent cerebral tumor surgery started to decline from day 1 after injury or surgery compared to control. This decreasing trend continued from day 3 (143.2±59.3 μmol/L, 188.8±49.4 μmol/L vs 287.3±80.2 μmol/L, p<0.0001) until day 7. No difference in urinary UA excretion was found in the TBI group or cerebral tumor surgery group. Urine allantoin and the allantoin to sUA ratio of the TBI group decreased on day 3 compared with the control group. The structural equation model showed that the sUA level was related to the Glasgow coma score (GCS) (r=0.5383, p<0.0001), suggesting the potential association of UA with consciousness level, as well as serum protein and electrolytes including albumin, calcium and phosphate.Conclusion:The sUA was decreased in patients with TBI or underwent cerebral tumor surgery.

Uric acid (UA) results from purine metabolism in hominoids. High serum uric acid (sUA), or hyperuricemia, is correlated with gout and many other diseases, including diabetes, hyperlipidemia, kidney diseases and cardiovascular diseases.1 Despite the adverse effects of high UA, studies have found that UA has strong endogenous antioxidant effects that protect against oxidative stress. The antioxidant action of UA was supported by evidence from neurodegenerative diseases, such as amyloidosis, Parkinson’s disease, and Alzheimer’s disease resulting from excessive oxidative damage.2-4Recently, new evidence on UA alterations in acute neuronal injury has emerged. It was found that administration of urate could reduce striatal or cortical damage and preserve neurological function in the context of cerebral ischemia.5,6 Although the precursor of UA, inosine, has been found to produce a better recovery from traumatic brain injury (TBI) in animal models with similar metabolic injury, the role of uric acid remains unclear. Some clinical studies on severe TBI as well as subarachnoid hemorrhage (SAH) patients identified decreased sUA in these patients,7,8 while other research mentioned increased sUA in patients with TBI.9 In patients with cerebral tumors, surgery may also trigger inflammatory and oxidative injuries resulting in neurological dysfunction. Whether UA levels change in patients undergoing cerebral tumor surgery is unclear.This study investigated changes in sUA in patients with TBI or patients after cerebral tumor surgery and the possible mechanism of these changes.